Phase 2 trial of cyclosporine-A, mycophenolate mofetil, and tocilizumab GVHD prophylaxis in cord blood transplantation

Double-unit cord blood transplantation (dCBT) has been associated with high rates of progression-free survival (PFS) in adults with hematologic malignancies but also with relatively high rates of acute graft-versus-host disease (aGVHD). We conducted a single-arm, phase 2 clinical trial that investigated the addition of tocilizumab, an interleukin-6 receptor blocker, to cyclosporine-A (CSA) and mycophenolate mofetil (MMF) for aGVHD prophylaxis after intermediate-intensity dCBT. A total of 45 patients (median age, 47 years; range, 27-60 years; 80% acute leukemia; median hematopoietic cell transplant-comorbidity index, 2) were enrolled from March 2018 to March 2021. Transplant outcomes were compared with 39 previous CSA and MMF dCBT controls with similar inclusion criteria. Tocilizumab recipients had less pre-engraftment syndrome (38%; 95% confidence interval [CI], 24-52 vs 72%; 95% CI, 54-84; P < .001) but inferior day 45 neutrophil engraftment (93%; median, 25.5 days vs 97%; median, 22 days; P = .009]. The primary end point of day 100 grade 2 to 4 aGVHD was no different between groups (71%; 95% CI, 55-82 with tocilizumab vs 82%; 95% CI, 65-91; P = .11). However, there was a trend toward a lower day 100 incidence of stage 1 to 4 lower gastrointestinal aGVHD with tocilizumab (16%; 95% CI, 7-28 vs 33%; 95% CI, 19-48; P = .059). There were no significant differences in the 3-year incidences of relapse, transplant-related mortality, PFS, or overall survival between the groups. Tocilizumab recipients exhibited a distinct pattern of gut microbiome disruption. In summary, tocilizumab-based GVHD prophylaxis delayed neutrophil recovery without a significant reduction in aGVHD and had no survival benefit after dCBT. Investigation of alternative strategies to prevent severe aGVHD after dCBT is warranted. This trial was registered at www.clinicaltrials.gov as #NCT03434730.